Using Pemetrexed via Ommaya Reservoir for Lung Cancer with Leptomeningeal Metastasis
A Open-label, Random, Multi-central Prospective Cohort of Observation Study on the Efficacy and Safety of Intraventricule Pemetrexed Disodium Via Ommaya Reservoir
This study is testing a new way to give a lung cancer drug directly to the brain to see if it helps people with cancer that has spread to the brain after other treatments didn't work.
Quick facts
| Study type | Observational |
|---|---|
| Enrollment | 64 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | Xiangya Hospital of Central South University Academic / other |
| Locations | 1 site (Changsha, Hunan) |
| Trial ID | NCT06399926 on ClinicalTrials.gov |
What this trial studies
This observational study evaluates the efficacy and safety of intraventricular pemetrexed disodium administered through an Ommaya reservoir in patients with leptomeningeal metastasis from lung cancer who have previously failed targeted therapies. Participants are assigned to two cohorts, receiving either 20mg of pemetrexed every 24 hours for 72 hours or 30mg once a week. The study includes an induction phase with efficacy evaluations every two cycles, followed by a consolidation phase if initial treatment shows positive results. The study aims to determine the best treatment approach based on efficacy and toxicity outcomes.
Who should consider this trial
Good fit: Ideal candidates are patients with confirmed non-squamous non-small cell lung cancer and leptomeningeal metastasis who have failed at least one line of targeted therapy.
Not a fit: Patients with leptomeningeal metastasis who have not undergone any prior targeted therapy may not benefit from this study.
Why it matters
Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with leptomeningeal metastasis from lung cancer who have limited treatment options.
How similar studies have performed: While similar approaches have been explored, this specific method of administering pemetrexed via an Ommaya reservoir is novel and has not been extensively tested in prior studies.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria:
1. confirmed pathologic diagnosis (histologic type of non-squamous non-small cell lung cancer in the primary lesion or metastatic lesion) with definitely genetic testing results (EGFR/ALK/ROS1);
2. In accordance with the CSCO Guidelines for the Diagnosis and Management of Central Nervous System Tumors, and the EANO-ESMO diagnostic criteria: a diagnosis of type I meningeal metastatic carcinoma is made when cerebrospinal fluid cytology testing reveals anisocytosis (3 consecutive tests are required if the cerebrospinal fluid cytology testing is initially negative for the patient) (one study showed that the specificity of anisocytosis in diagnosing meningeal metastases in patients with solid tumors was 100%) or meningeal lesions Biopsy confirms the diagnosis. (Type IIA-C meningeal metastases: negative or atypical cerebrospinal fluid cytology, MRI showing linear or/and nodular meningeal enhancement\^ with typical clinical symptoms\*).
* MRI: at least 1.5T; demonstrates sulcal, smear, or linear ventricular enhancement, cranial nerve root enhancement or nodular meningeal enhancement, or cauda equina spinal enhancement; control enhancement T1-weighted sequences and Flair sequences; nodularity is defined as foci of ≥ 5x10mm enhancement; sequences of choice: cranial planar enhancement + T2Flair (enhancement) or and total spinal planar enhancement (when suspicion of spinal involvement); 3D T1 enhancement (involved cranial nerves - optional); cerebrospinal fluid flow imaging (functional or anatomic).
* Typical clinical manifestations: headache, nausea, vomiting; epilepsy; mental changes, gait difficulties; cranial nerve damage (diplopia, visual abnormalities, hearing abnormalities, facial nerve palsy, difficulty chewing, difficulty swallowing, choking, etc.); neurogenic signs (cauda equina symptoms, mainly perineal numbness, tingling, defecation and urination disturbances, weakness or incomplete paralysis of both lower limbs); sensorimotor defects of the limbs; cervical back Radicular pain; be careful to differentiate from signs and symptoms of brain parenchymal metastases, extracranial disease, treatment-related adverse effects, and non-tumor comorbidities.
3\. Based on the guideline-driven first-line choice of TKI agents for gene-positive patients, enrolment would therefore require: failure of at least three generations of EGFR-TKIs for patients with EGFR mutations; failure of at least second-generation ALK inhibitors for ALK mutations; and failure of at least one ROS1 inhibitor for ROS1 mutations.
4\. No contraindication to Ommaya capsule implantation. 5. Female subjects who are capable of becoming pregnant must agree to use reliable contraception throughout the trial; male subjects whose female partner is capable of becoming pregnant must agree to use reliable contraception throughout the trial.
6\. patients must sign an informed consent form and must be willing and able to comply with visits, treatment regimens, laboratory tests and other requirements as specified in the study protocol
Exclusion Criteria:
1. HBsAg-positive patients may be enrolled, but patients with higher than normal viral copy number or HBcAb-positive patients should receive effective anti-HBV treatment until 6 months after the end of the trial. HCV RNA carriers may be enrolled, but need to receive effective anti-HCV treatment throughout the trial, and continue to receive effective anti-HCV treatment until 6 months after the end of the trial.
2. human immunodeficiency virus (HIV) infection.
3. significant extracranial lesion progression or extensive extracranial lesions causing severe symptoms that cannot be effectively treated.
4. patients with extreme emaciation or cachexia.
5. Extensive parenchymal brain lesions with severe symptoms that cannot be effectively treated.
6. patients with other malignant tumors that are currently undergoing treatment.
7. have received or will receive a live vaccine within 30 days prior to signing the informed consent form.
8. other conditions that, in the judgment of the investigator, may affect subject safety or trial compliance, including symptomatic heart failure, unstable angina, myocardial infarction, active infections (including tuberculosis infections) requiring systemic therapy; or severe organ dysfunction, with creatinine clearance \<45 ml/min calculated from glomerular filtration rate by the Cockcroft-Gault formula or by the Tc99m-DPTA serum clearance method; an absolute neutrophil count \<0.5 x 109/L; a platelet count \<25 x 109/L, or in patients with severe active visceral bleeding; or severe Abnormal liver function (bilirubin greater than 3.0 times upper limit of normal; AST and ALT greater than 5.0 times upper limit of normal).
9. patients with known hypersensitivity to pemetrexed with a history of serious adverse reactions, and patients with potentially life-threatening conditions for reuse.
10. pregnant or lactating women.
Where this trial is running
Changsha, Hunan
- Xiangya Hospital Central South University — Changsha, Hunan, China (Recruiting)
Study contacts
- Principal investigator: bin Li, doctor — Xiangya Hospital of Central South University
- Study coordinator: bin Li, doctor
- Email: bincsuxy@csu.edu.cn
- Phone: 13467713587
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.